Accelerated stability study of the ester prodrug remdesivir: Recently FDA‐approved Covid‐19 antiviral using reversed‐phase‐HPLC with fluorimetric and diode array detection
| Autor: | Mohamed M.A. Hamdy, Mona M. Abdel Moneim, Miranda F. Kamal |
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| Rok vydání: | 2021 |
| Předmět: |
Acetonitriles
Hot Temperature Clinical Biochemistry Antiviral Agents Biochemistry Dosage form Analytical Chemistry chemistry.chemical_compound Hydrolysis Drug Stability Limit of Detection Drug Discovery Humans Prodrugs Acetonitrile Molecular Biology Phosphoric acid Chromatography High Pressure Liquid Pharmacology Chromatography Reverse-Phase Alanine Photolysis Chromatography General Medicine Reversed-phase chromatography Fluorescence Adenosine Monophosphate COVID-19 Drug Treatment chemistry Distilled water Degradation (geology) Oxidation-Reduction |
| Zdroj: | Biomedical Chromatography. 35 |
| ISSN: | 1099-0801 0269-3879 |
| DOI: | 10.1002/bmc.5212 |
| Popis: | Remdesivir (RDV) is the first antiviral drug, approved by the Food and Drug Administration, to treat severe acute respiratory syndrome coronavirus 2. RDV is a relatively new chemical entity, 'ester prodrug', with no reported stability profile. Due to the urgency of its use and thus fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried out on a C18 column (250 × 4.6 mm, 5 µm) with dual detection: diode array at 240 nm and fluorescence at λex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in the ratio of 55:45 (v/v), respectively, was used. The linearity range using HPLC-diode array detection was 0.1-15 µg/mL, whereas that using fluorimetric detection was 0.05-15 µg/mL. As per the International Conference on Harmonization guidelines, RDV has been degraded by accelerated alkaline, acidic, neutral hydrolysis, oxidative, heat, and photolytic stress conditions. Possible degradation hypothesis of the parent molecule has been suggested and illustrated. The proposed methods have achieved selective determination of the intact drug with no peaks overlapping in all assumptions. Extensive degradation confirms threatened drug stability at thermal and basic hydrolytic stressing. The developed methods were fully validated and proved suitable for quality control routine analysis of RDV in raw material and pharmaceutical dosage forms. |
| Databáze: | OpenAIRE |
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